The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Khalid El Bairi, Harry R. Haynes, The International Immuno-Oncology Biomarker Working Group, Elizabeth Blackley, Susan Fineberg, Jeffrey Shear, Sophia Turner, Juliana Ribeiro de Freitas, Daniel Sur, Luis Claudio Amendola, Masoumeh Gharib, Amine Kallala, Indu Arun, Farid Azmoudeh-Ardalan, Luciana Fujimoto, Luz F. Sua, Shi Wei Liu, Huang Chun Lien, Pawan Kirtani, Marcelo BalancinHicham El Attar, Prerna Guleria, Wenxian Yang, Emad Shash, I. Chun Chen, Veronica Bautista, Jose Fernando Do Prado Moura, Bernardo L. Rapoport, Carlos Castaneda, Eunice Spengler, Gabriela Acosta-Haab, Isabel Frahm, Joselyn Sanchez, Miluska Castillo, Najat Bouchmaa, Reena R. Md Zin, Ruohong Shui, Timothy Onyuma, Wentao Yang, Zaheed Husain, Karen Willard-Gallo, An Coosemans, Edith A. Perez, Elena Provenzano, Paula Gonzalez Ericsson, Eduardo Richardet, Marleen Kok, Marleen Kok, Sean Hall, Peter Vermeulen, Tessa Steenbruggen, Sandra Demaria, Sherene Loi

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The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Original languageEnglish
Article number150
Journalnpj Breast Cancer
Issue number1
Publication statusPublished - 1 Dec 2021

Bibliographical note

Funding Information:
Shom Goel’ work is supported by the National Health and Medical Research Council of Australia (Investigator Grant GNT1177357 to S.G.); Susan G. Komen for the Cure (CCR18547966 to S.G.); the Royal Australasian College of Physicians (Research Establishment Fellowship to S.G.); and the NIH/NCI (P50 CA168504 to S.G.). Sherene Loi is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. Khalid El Bairi would like to report that the content of this review reflects the authors’ perspectives and not of his institution and/or affiliation. Roberto Salgado is supported by the Breast Cancer Research Foundation (BCRF, grant N° 17-194).

Funding Information:
In the United States, the PD-L1 SP142 assay has been approved as a companion assay for the selection of patients with TNBC to offer atezolizumab and taxane chemotherapy ( foreningar/uploads/L15178/kvast/brostpatologi/Brostjuni2020.pdf). In Brazil, some central pathology laboratories perform PD-L1 testing based on principal investigator-sponsored agreements. PD-L1 IHC is tested mostly in private institutions with some programs offering pro bono testing to assess eligibility for approved ICI. The Brazilian Pathology Society follows WHO recommendations; hence the inclusion of TILs in daily practice can be envisaged in the near future. In Chile, PD-L1 testing is available on several platforms but their cost is high and this is not covered by public health insurance which covers 75% of the population. Anti-PD-L1 drugs remain at a high cost and are usually only funded by additional insurance or in clinical trial settings. In Argentina, PD-L1 testing is not covered by public funds. A few central private pathology laboratories perform PD-L1 testing on-demand funded by industry. Some pathologists have started to incorporate TILs into pathology reports for TNBC; however, there are no current national guidelines. In Perú, TILs evaluation has been included in TNBC protocols by pathologists in public and private centers. SP142 IHC is available in a few private labs while Dako 22C3 is being processed for non-breast malignancies in private and public centers. There are a few BC patients who have received atezolizumab funded via private insurance or clinical trials. It is not expected that the public system will support anti-PD-1 drugs in the near future.

Publisher Copyright:
© 2021, The Author(s).


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